| 1 | Allogeneic gene-edited HIV-specific CAR-T cells secreting PD-1 blocking scFv enhance specific cytotoxic activity against HIV Envt cells in vivo显示文摘HIV-specific chimeric antigen receptor(CAR)T-cells have been developed to target HIV-1 infected CD4t T-cells that express HIV Env proteins.However,T cell exhaustion and the patient-specific autologous paradigm of CAR-T cell hurdled clinical applications.Here,we created HIV-specific CAR-T cells using human peripheral blood mononuclear cells and a 3BNC117-E27(3BE)CAR construct that enabled the expression of programmed cell death protein(PD-1)-blocking scFv E27 and the single-chain variable fragment of the HIV-1-specific broadly neutralizing antibody 3BNC117 to target native HIV Env.Compared with T cells expressing 3BNC117-CAR alone,3BE CAR-T cells showed greater cytotoxic activity against HIV Envt cells with stronger proliferation capability,higher killing efficiency,and enhanced cytokine secretion in the presence of HIV Env-expressing cells.Furthermore,we manufactured TCR-deficient 3BE CAR-T cells through gene editing and demonstrated that these CAR-T cells could effectively kill HIV Env^(+) cells in vivo without the occurrence of severe graft-versus-host disease(GvHD)in NSG mice.These data suggest that we have provided a feasible approach to the generation of“off-theshelf”anti-HIV CAR-T cells in combination with PD-1 checkpoint blockade immunotherapy,which can be a powerful therapeutic candidate for the functional cure of HIV. | Hanyu Pan Xinyi Yang Jing Wang Huitong Liang Zhengtao Jiang Lin Zhao Yanan Wang Zhiming Liang Xiaoting Shen Qinru Lin Yue Liang Jinglong Yang Panpan Lu Yuqi Zhu Min Li Pengfei Wang Jianqing Xu Hongzhou Lu Huanzhang Zhu | 2023 | Virologica Sinica2023，38，2： | 0 |
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